Ishiyama-Shigemoto S, Yamada K, Yuan X, Ichikawa F, Nonaka K
Department of Medicine, Kurume University School of Medicine, Japan.
Diabetologia. 1999 Jan;42(1):98-101. doi: 10.1007/s001250051120.
To assess the role of polymorphisms in the beta2-adrenergic receptor gene in the development of obesity and obesity-related metabolic disorders, we analysed Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in 400 non-obese subjects (body mass index < 27 kg/m2) and 108 obese subjects (body mass index> or =27 kg/m2). The Gln27Glu substitution was twice as common in obese subjects as in non-obese subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.14, 95 % confidence interval 1.35-3.41). The frequency of the Glu27 allele was also higher in patients with Type II (non-insulin-dependent) diabetes mellitus than nondiabetic subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.13, 95% confidence interval 1.34-3.41). Analysis of variance of multiple variables showed an association between 2-h post-load glucose concentrations and body mass index but not with the Glu27 variant, suggesting that the association with diabetes could be secondary to obesity. Obese subjects carrying the variant allele had higher concentrations of serum triglyceride than obese subjects homozygous for the wild type allele (2.68+/-1.90 vs 1.18+/-1.15 mmol/l, p = 0.02). Conversely, the frequency of Gly16 homozygotes was lower in obese women when compared with non-obese women (11% vs 28%, p = 0.01, odds ratio 0.30, 95% confidence interval 0.12-0.75), although the association was not present in male subjects. Thr164Ile substitution was not detected in the subjects of this study. These observations suggest that the amino-terminal polymorphisms of the beta2-adrenergic receptor gene could be involved in the molecular pathogenesis of obesity and hypertriglyceridaemia, and thereby the development of Type II diabetes mellitus.
为评估β2 - 肾上腺素能受体基因多态性在肥胖症及肥胖相关代谢紊乱发生发展中的作用，我们分析了400名非肥胖受试者（体重指数<27kg/m²）和108名肥胖受试者（体重指数≥27kg/m²）的Arg16Gly、Gln27Glu和Thr164Ile多态性。Gln27Glu替代在肥胖受试者中的出现频率是非肥胖受试者的两倍（0.14对0.07，p = 0.001，优势比2.14，95%置信区间1.35 - 3.41）。Glu27等位基因在II型（非胰岛素依赖型）糖尿病患者中的频率也高于非糖尿病受试者（0.14对0.07，p = 0.001，优势比2.13，95%置信区间1.34 - 3.41）。多变量方差分析显示，负荷后2小时血糖浓度与体重指数之间存在关联，但与Glu27变异无关联，这表明与糖尿病的关联可能继发于肥胖。携带变异等位基因的肥胖受试者血清甘油三酯浓度高于野生型等位基因纯合的肥胖受试者（2.68±1.90对1.18±1.15mmol/L，p = 0.02）。相反，与非肥胖女性相比，肥胖女性中Gly16纯合子的频率较低（11%对28%，p = 0.01，优势比0.30，95%置信区间0.12 - 0.75），尽管男性受试者中不存在这种关联。本研究受试者中未检测到Thr164Ile替代。这些观察结果表明，β2 - 肾上腺素能受体基因的氨基末端多态性可能参与肥胖症和高甘油三酯血症的分子发病机制，进而参与II型糖尿病的发生发展。
